The main objectives of the proposed study are to evaluate the contribution of sterol to the structure and functions of plasma membranes and to the growth and proliferation of animal cells. The sterol component of the plasma membrane of cells growing in chemically defined media will be manipulated in the following way: (1) the sterol concentration will be altered quantitatively by specifically blocking sterol synthesis de novo or by supplementing the culture medium with sterols. (2) The sterol composition will be altered qualitatively by stopping sterol synthesis and at the same time providing sterols of varying structure in the medium. The effects of altering the sterol composition upon membrane structure and fluidity will be examined, employing techniques such as paramagnetic quenching of fluorescence, etc. Effects upon membrane function will be examined in studies of the cellular uptake of nutrients and ions and of the activities of several membrane localized enzymes. Effects upon cell growth and proliferation will be analyzed in studies of growth pattern and of rates of protein and nucleic acid synthesis. The relationship between sterol synthesis and mitogenesis of lymphocytes in response to plant lectins and the nature of elevated sterol production associated with leukemogenesis will be studied. The membrane sterol composition of normal and malignant lymphatic cells will be compared and the effects of abnormal sterol composition upon the function of malignant cells will be investigated.